POS0683 EFFICACY AND SAFETY OF UPADACITINIB IN TNFi-IR PATIENTS WITH RHEUMATOID ARTHRITIS FROM THREE PHASE 3 CLINICAL TRIALS
Authors: R. M. Fleischmann, L. Bessette, J. Sparks, S. Hall, M. Jain, A. Kakehasi, Y. Song, S. Meerwein, R. Demasi, J. Suboticki, A. Rubbert-Roth
Journal: Annals of the Rheumatic Diseases (2022)

Background For patients with RA who are refractory to biologic DMARDs (bDMARDs), such as tumor necrosis factor inhibitors (TNFis), optimal disease control is less likely to be achieved with subsequent therapy. 1 In line with recommendations from EULAR and ACR, switching to a treatment with a different mechanism of action is appropriate for these patients. Objectives To describe the efficacy and safety of upadacitinib (UPA) 15 mg once daily in patients with RA and an inadequate response or intolerance to TNFis (TNFi-IR). Methods A post hoc subgroup analysis was conducted in TNFi-IR patients who were treated with UPA 15 mg once daily in three Phase 3 clinical trials: SELECT-BEYOND, 2 -CHOICE, 3 and -COMPARE. 4 For COMPARE, only patients treated with adalimumab and switched to UPA as rescue therapy were included. ≥20/50/70% improvement in ACR criteria, DAS28(CRP), CDAI, and SDAI, as well as change from baseline in HAQ-DI and other patient-reported outcomes (PROs) were reported through 24 weeks. Non-responder imputation was used for all missing categorical outcomes; as observed (COMPARE) or multiple imputation (CHOICE, BEYOND) were used for missing continuous outcomes. Pooled safety results were presented as exposure-adjusted event rates (EAERs) with a cut-off of June 30, 2021. Results 568 TNFi-IR patients were included: 146 from BEYOND, 263 from CHOICE, and 159 from COMPARE. Mean duration since RA diagnosis was longer for BEYOND and CHOICE versus COMPARE; cardiovascular (CV) risk factors were common among this refractory population (Table 1). ACR20/50/70 and disease activity outcomes observed in the TNFi-IR population were generally consistent with the overall BEYOND 2 and CHOICE 3 bDMARD-IR populations, and consistent across the three studies in the TNFi-IR subgroups (Figure 1). Improvements in PROs including HAQ-DI, fatigue, pain, and morning stiffness over 24 weeks were observed (data not shown). Pooled safety results reporting 1574.8 patient-years (PY) of exposure in the TNFi-IR subgroup showed similar results to the overall BEYOND 2 and CHOICE 3 bDMARD-IR study populations, with EAERs of 3.1 events/100 PY for herpes zoster and 0.8 events/100 PY for adjudicated major adverse CV events, adjudicated venous thromboembolism (VTE), and malignancy excluding non-melanoma skin cancer. The EAER of any AE leading to death was 1.4 events/100 PY. Table 1. Baseline characteristics of TNFi-IR patients treated with UPA 15 mg n (%), unless specified SELECT-BEYOND (n=146) SELECT-CHOICE (n=263) SELECT-COMPARE (ADA → UPA) (n=159) Female 122 (83.6) 219 (83.3) 133 (83.6) Mean (SD) age, years 56.6 (11.0) 55.5 (11.1) 53.9 (10.6) Mean (SD) duration of RA diagnosis, years 13.2 (9.5) 12.5 (9.4) 8.2 (8.5) Concomitant csDMARDs MTX alone 100 (70.4) 195 (74.1) 159 (100.0) MTX and other csDMARDs 20 (14.1) 25 (9.5) 0 csDMARDs other than MTX 22 (15.5) 38 (14.4) 0 Concomitant oral steroids 73 (50.0) 140 (53.2) 98 (61.6) 1 prior bDMARD 68 (46.6) 172 (65.4) 142 (89.3) 2 prior bDMARDs 40 (27.4) 62 (23.6) 17 (10.7) a ≥3 prior bDMARDs 38 (26.0) 29 (11.0) 0 Failed ≥1 prior TNFi due to lack of efficacy b 131 (89.7) 223 (84.8) 159 (100.0) History of VTE / CV event 3 (2.1) / 28 (19.2) 6 (2.3) / 20 (7.6) 4 (2.5) / 14 (8.8) CV risk factors Hypertension 72 (49.3) 109 (41.4) 68 (42.8) Diabetes mellitus 22 (15.1) 34 (12.9) 17 (10.7) Smoking (current former past) 68 (46.6) 109 (41.5) 55 (34.6) Elevated LDL-C (≥3.36 mmol/L) 38 (26.0) 52 (20.0) 48 (30.2) Low HDL-C (≤1.55 mmol/L) 80 (54.8) 171 (65.0) 88 (55.3) a These patients received one bDMARD before entry into SELECT-COMPARE. b Remaining patients were intolerant to ≥1 prior TNFi. Conclusion In this post hoc subgroup analysis, TNFi-IR patients treated with UPA 15 mg achieved clinically meaningful efficacy responses over 24 weeks, with safety consistent with the overall bDMARD-IR patient population in the Phase 3 program. References [1]Rendas-Baum R, et al. Arthritis Res Ther 2011;13:R25; [2]Genovese C, et al. Lancet 2018;391:2513–24; [3]Rubbert-Roth A, et al. NEJM 2020;383:1511–21; [4]Fleischmann R, et al. Ann Rheum Dis 2019;78:1454–62. Acknowledgements AbbVie funded this study; contributed to its design; participated in data collection, analysis, and interpretation of the data; and participated in the writing, review, and approval of the abstract. AbbVie and the authors thank all study investigators for their contributions and the patients who participated in this study. No honoraria or payments were made for authorship. Medical writing support was provided by Amy Wilson, MSc, of 2 the Nth (Cheshire, UK), and was funded by AbbVie. Disclosure of Interests Roy M. Fleischmann Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Galvani, Gilead, GSK, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Biosplice, Bristol-Myers Squibb, Flexion, Gilead, Horizon, Eli Lilly, Galvani, Janssen, Novartis, Pfizer, Sanofi-Aventis, Selecta, Teva, UCB, Viela, and Vorso, Louis Bessette Speakers bureau: AbbVie, Amgen, Bristol-Meyers Squibb, Celgene, Eli Lilly, Fresenius Kabi, Gilead, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, Teva, and UCB, Consultant of: AbbVie, Amgen, Bristol-Meyers Squibb, Celgene, Eli Lilly, Fresenius Kabi, Gilead, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, Teva, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Meyers Squibb, Celgene, Eli Lilly, Fresenius Kabi, Gilead, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, Teva, and UCB, Jeffrey Sparks Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer, Stephen Hall Consultant of: AbbVie, Amgen, Bristol-Meyers Sqibb, Eli Lilly, Gilead, Janssen, Merck, Novartis, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Meyers Sqibb, Eli Lilly, Gilead, Janssen, Merck, Novartis, and UCB, Manish Jain Consultant of: AbbVie, Amgen, Eli Lilly, Novartis, and Pfizer, Grant/research support from: AbbVie, Amgen, Eli Lilly, Novartis, and Pfizer, Adriana Kakehasi Speakers bureau: AbbVie, Amgen, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer, Sandoz, and UCB, Consultant of: AbbVie, Amgen, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer, Sandoz, and UCB, Grant/research support from: AbbVie, Amgen, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer, Sandoz, and UCB, Yanna Song Shareholder of: AbbVie (may own stock or options), Employee of: AbbVie, Sebastian Meerwein Shareholder of: AbbVie (may own stock or options), Employee of: AbbVie, Ryan DeMasi Shareholder of: AbbVie (may own stock or options), Employee of: AbbVie, Jessica Suboticki Shareholder of: AbbVie (may own stock or options), Employee of: AbbVie, Andrea Rubbert-Roth Consultant of: AbbVie, AbbVie Deutschland, Amgen, Bristol-Myers Squibb, Chugai Pharmaceuticals, Eli Lilly, F. Hoffman-La Roche, Gilead Sciences, Janssen Global Services, Novartis, and Sanofi Pasteur